TW201537167A - An inspecting equipment and a biochip - Google Patents

Abstract

An inspecting equipment includes a biochip and a processing unit. The biochip includes a micro electrode dot array, a cover, a shielding layer, N control unit, and a bonding area. The micro electrode dot array includes N micro electrodes. N control unit are disposed under N micro electrodes respectively and connected as daisy-chain. The shielding layer is disposed between the micro electrode dot array and N control unit to isolate electrical interference from the cover. The processing unit makes the biochip to actuate and detect droplet(s) based on a data input signal, a data output signal, a clock signal, a first control signal, a second control signal, and a third control signal.

Description

Biodetection equipment and biochip

The present invention relates to a biodetection device and a biochip, and more particularly to a biodetection device and a biochip having an array of microelectrode dots.

As the average life expectancy of Chinese people increases year by year, the importance of health checks has increased year by year, whether for disease screening, medical diagnosis or aged care. The conventional analysis method is to separate the sample using a centrifuge, take out the portion to be detected, and then add a different reagent reactant, and judge the condition of the sample according to the color of the substance or the concentration of the product. Therefore, the manpower required is long and the analysis time is long, resulting in high costs.

In contrast, the development of biochips can not only achieve rapid and effective analysis, but also can be used at home, reducing labor costs, and can be widely used. The laboratory-on-a-chip (LOC) in biochips, also known as the Micro Total Analytical System (μTAS), is a micro-integration process that is originally integrated into the laboratory. Wafer. In addition to shortening the overall reaction time and improving efficiency, laboratory wafers have also greatly reduced inspection errors. This design combines medical analysis and electronic systems to save time, space and human resources. The cost reduction is definitely a high-profile technology and product in the future.

Most of the traditional laboratory wafers use glass sheets as substrates. Based on Micro-electro-mechanical system (MEMS) technology, combined with semiconductor manufacturing process, a complex set of micro-channels and micro-controls are planned on the wafer. The valve member of the flow channel, together with the external pressurizing device and the inspection device, completes a platform for complete processing and analysis of the sample. On this platform, it is possible to provide separation and purification of the sample, mixing of the sample and the reagent, and determination of the result.

However, for laboratory wafers using microchannels and valve controls, there are many problems at the system level:

1. Due to the difficulty of heterogeneous integration, the control and detection components of the laboratory wafer must be external. In general, if there are too many external control components, the number of input and output electrical signals will be too much, and the area of the laboratory wafer will be limited.

2. Most microchannels are pressurized by an external pump, allowing the liquid in the microchannel to flow from a high pressure to a low pressure. However, because the microchannel is a confined space, when the pump generates air pressure, the droplets will flow around, and the droplets cannot be effectively driven, resulting in waste of the specimen and reduced sensitivity in analysis.

3. Since the microchannels on the wafer have been systematically planned, the analysis of different experiments will require different microchannel lab wafers, thus causing personnel to learn the operation of biochips with different microchannels. The complexity of the operation is increased, the training cost of the personnel is also increased, and the product development cost is also increased.

4. There are many ways to control the liquid in the micro flow channel. Kinds, such as pressure, temperature, etc., but no matter which control method is adopted, there is no mechanism for reading back, which causes experimental errors.

Accordingly, it is an object of the present invention to provide a biodetection device and a biochip having a small number of input and output signals, an effective driving and sensing sample, and a readback mechanism.

Thus, the biodetection device of the present invention comprises a biochip and a processing unit.

The biochip includes a microelectrode dot array, a cover, a shielding layer, and N daisy chained control units.

The microelectrode dot array includes N microelectrodes, N is an integer and N>1, and the N microelectrodes are arranged at intervals.

The cover is disposed above the array of microelectrode dots and receives a bias signal and includes a droplet space to accommodate the droplets.

The shielding layer is disposed under the array of microelectrode dots to isolate electromagnetic interference from the cover to be transmitted thereto.

The N daisy chain connected control unit is disposed under the shielding layer without electromagnetic interference from the cover body, and each control unit is located below the corresponding microelectrode, and each of the electrical connections corresponds to The microelectrode is configured to provide a microelectrode signal to the corresponding microelectrode, and each control unit receives a clock signal, a first to third control signal, and selects one according to the clock signal and the first control signal. An input signal or a measurement signal related to the microelectrode signal as an output signal, wherein an input signal received by a first one of the N control units is used For driving the data input signal of the droplet, each of the remaining N-1 control units receives an output signal from its previous control unit.

Each control unit further changes the microelectrode signal provided by the second and third control signals and the output signal, and uses the differential pressure between the microelectrode signal and the bias signal between the different control units to drive the cover. Droplets in the droplet space of the body.

The processing unit is electrically connected to the N control units, and generates the data input signal, the clock signal, the first control signal, the second control signal, and the third control signal, and receives a data output signal, where the data signal is from An output signal of the Nth control unit of the N control units, and operating the biochip according to the clock signal, the first control signal, the second control signal, the third control signal, and the data output signal The mode is sensed to sense the position of the drop.

The effect of the invention is that the control unit under each microelectrode of the microelectrode dot array is connected in series by a daisy chain, also called a scan chain, to achieve less input and output signals and effective driving. Biodetection devices and biochips that sense the sample and have a readback mechanism.

1‧‧‧Biochip

11‧‧‧Microelectrode dot array

12‧‧‧ Cover

121‧‧‧First dielectric layer

122‧‧‧Second dielectric layer

123‧‧‧ Third dielectric layer

124‧‧‧ first surface

125‧‧‧ second surface

126‧‧‧ third surface

127‧‧‧hydrophobic layer

128‧‧‧ Droplet space

13‧‧‧Shield

14‧‧‧Line area

141‧‧‧data input pad

142‧‧‧ data output pad

143‧‧‧clock pad

144‧‧‧First control pad

145‧‧‧Second control pad

146‧‧‧ third control pad

151‧‧‧First multiplexer

152‧‧‧D type flip-flop

153‧‧‧Anti-gate

154‧‧‧Second multiplexer

155‧‧‧ third multiplexer

156‧‧‧First transistor

157‧‧‧second transistor

158‧‧‧ Third transistor

159‧‧‧First reverser gate

160‧‧‧Second reverser gate

161‧‧‧Anti-gate

162‧‧‧Switching elements

2‧‧‧Processing unit

7‧‧‧ droplets

E1~E900‧‧‧Microelectrode

CU1~CU900‧‧‧Control unit

C1‧‧‧ first control signal

C2‧‧‧second control signal

C3‧‧‧ third control signal

N1‧‧‧ first intermediate signal

N2‧‧‧ second intermediate signal

N3‧‧‧ third intermediate signal

Nd‧‧‧Common joint

CLK‧‧‧ clock signal

SI‧‧‧ input signal

SO‧‧‧ output signal

V1‧‧‧ first reference voltage

V2‧‧‧second reference voltage

Other features and effects of the present invention will be apparent from the following description of the drawings, wherein: FIG. 1 is a top view showing a preferred embodiment of the biological testing device of the present invention; FIG. 2 is a schematic cross-sectional view Figure 1 illustrates the preferred embodiment; 3 is a circuit diagram showing the control unit of the preferred embodiment; FIG. 4 is a top plan view showing the droplet distribution pattern in the preferred embodiment; FIG. 5 is a timing chart illustrating the preferred embodiment. The signal relationship in a sensing mode; and FIG. 6 is a timing diagram, and FIG. 5 illustrates the preferred embodiment.

1 and FIG. 2, FIG. 2 is a cross-sectional view of the II of FIG. 1. The preferred embodiment of the biodetection apparatus of the present invention comprises a biochip 1 and a processing unit 2. The biochip 1 includes a microelectrode dot array 11, a cover 12, a shielding layer 13, N control units CU1 CU900, and a bonding area 14, N being an integer and N>1.

The microelectrode dot array 11 includes N microelectrodes E1 to E900, and the N microelectrodes E1 to E900 are arranged at intervals. In this embodiment, N=900, each of the microelectrodes E1 to E900 is square, and the 900 microelectrodes E1 to E900 are arranged in a 30×30 square array of microelectrode dots 11 . In other embodiments, N The microelectrodes may also be arranged in any other shape, and each microelectrode may also be hexagonal, other polygonal, circular or irregular.

The cover 12 is disposed above the microelectrode dot array 11 and includes a first dielectric layer 121, a second dielectric layer 122 disposed above the first dielectric layer 121, and two hydrophobic layers. A hydrophobic layer 127, a third dielectric layer 123, and a droplet space 128. The first dielectric layer 121 has a first surface 124, the first The second dielectric layer 122 has a second surface 125 and a third surface 126 on opposite sides. The first surface 124 and the second surface 125 are located between the first dielectric layer 21 and the second dielectric layer 122. The two hydrophobic layers 127 are respectively formed on the first surface 124 of the first dielectric layer 121 and the second surface 125 of the second dielectric layer 122. The droplet space 128 is between the two hydrophobic layers 127 for receiving A droplet 7, which is a sample.

In the embodiment, the first dielectric layer 121 is used to protect the microelectrode dot array 11 to avoid oxidation, and the microelectrode dot array 11 is prevented from contacting the droplet 7. The material of the second dielectric layer 122 is glass, and the material of the third dielectric layer 123 is indium tin oxide (ITO). The material of the two hydrophobic layer 127 is Teflon, so that the friction between the two hydrophobic layers 127 and the droplets 7 located in the droplet space 128 is small and is relatively easy to drive.

The shielding layer 13 is disposed under the microelectrode dot array 11 for insulating electromagnetic interference from the cover 12 to be transmitted below the shielding layer 13. The shielding layer 13 can receive a fixed voltage, maintain its voltage level at a fixed potential, and maintain a floating state.

The 900 control units CU1 CU 900 are respectively disposed under the 900 microelectrodes E1 EE900 and below the shielding layer 13 , and the shielding layer 13 is used to isolate electromagnetic interference from the cover 12 . The 900 control units CU1 to CU900 are electrically connected to the 900 microelectrodes E1 to E900, respectively, and the control units CU2 to CU900 are electrically connected to the previous control units CU1 to CU899, respectively. Each control unit CU1~CU900 receives an input signal SI, a clock signal CLK, a first control signal C1, a second control signal C2, and a third control signal C3, and outputs an output signal. No. SO, and a microelectrode signal is output to the corresponding microelectrodes E1 to E900. The input signal SI received by the control unit CU1 is a data input signal, and the input signals SI of the control units CU2 CU900 are the output signals SO from the previous control units CU1 CU CU 899 respectively, so that the control units CU1 〜 The CU 900 forms a daisy chain or a scan chain in series.

Referring to FIG. 3, FIG. 3 is a circuit diagram of each control unit CU1~CU900. Each control unit CU1~CU900 includes a first multiplexer 151, a D-type flip-flop 152, an inverse gate 153, and a second. A multiplexer 154, a third multiplexer 155, a first transistor 156, a second transistor 157, a third transistor 158, a first inverter gate 159, and a second inverter gate. 160, a reverse gate 161, and a switching element 162.

The first multiplexer 151 has a first input end, a second input end, a selection end, and an output end. Each first multiplexer 151 receives an input signal SI from the corresponding control unit CU1 CU900, the first control signal C1, and a measurement signal, and according to the first control signal C1, the first control signal When the logic value of C1 is 1, the measurement signal is output to the output terminal, and when the logic value of the first control signal C1 is 0, the input signal SI is output to the output terminal.

The D-type flip-flop 152 has a data end electrically connected to the output end of the first multiplexer 151, a clock end, and an output end. The D-type flip-flop 152 receives the signal from the output end of the first multiplexer 151 and the clock signal CLK, and according to the clock signal CLK, when triggered by the positive edge of the clock signal CLK, the first The logic value of the signal at the output of the tool 151 is stored in the D-type flip-flop 152 and output as the output. The signal SO is at the output.

The anti-gate 153 has a first input end, a second input end, and an output end. The inverse gate 153 receives the second control signal C2 and the third control signal C3, respectively, and performs a NOR logic operation, and outputs the result to the output terminal.

The second multiplexer 154 has a first input end electrically connected to the output end of the D-type flip-flop 152, a second input end electrically connected to the output end of the inverse-gate 153, a selection end, and a An output of a first intermediate signal n1 is generated. The second multiplexer 154 receives the output signal SO from the D-type flip-flop 152, the second control signal C2, and a signal from the output of the inverse gate 153, and according to the second control signal C2, When the logic value of the second control signal C2 is 1, the output signal SO is output as the first intermediate signal n1, and when the logic value of the second control signal C2 is 0, the output of the inverse gate 153 is The signal output is the first intermediate signal n1.

The third multiplexer 155 has a first input end receiving a first reference voltage V1, a second input end electrically connected to the output end of the second multiplexer 154, a selection end, and a generation The output of the second intermediate signal n2. The third multiplexer 155 receives the first reference voltage V1, the first intermediate signal n1 from the second multiplexer 154, and the second control signal C2, and according to the second control signal C2, When the logic value of the second control signal C2 is 1, the logic value 1 represented by the first reference voltage V1 is output as the second intermediate signal n2, and when the logic value of the second control signal C2 is 0, the first An intermediate signal n1 is output as the second intermediate signal n2.

The first transistor 156, the second transistor 157, and the third transistor 158 are sequentially connected in series between the first reference voltage V1 and a second reference voltage V2, and respectively respond to the third The second intermediate signal n2 of the workpiece 155, the second control signal C2, and the first intermediate signal n1 from the second multiplexer 154 are respectively turned on or off. In this embodiment, the first transistor 156 and the second transistor 157 are both a P-type metal oxide semiconductor (PMOS), and the third transistor 158 is an N-type metal oxide semiconductor (NMOS). The first reference voltage V1 is VDD, the second reference voltage V2 is a ground point (Ground), and the first reference voltage V1 is greater than the second reference voltage V2.

The first inverter gate 159 has an input terminal electrically connected to the output end of the second multiplexer 154, and an output end. The first inverter gate 159 receives the first intermediate signal n1 from the second multiplexer 154, and reverses the logic value of the first intermediate signal n1, and outputs the output signal to the output terminal.

The anti-gate 161 has a first input end electrically connected to the output end of the first inverter gate 159, a second input end, and an output end generating a third intermediate signal n3. The NAND gate 161 receives the signal from the output end of the first inverter gate 159, and the second control signal C2, and performs NAND logic operation, and outputs the third intermediate signal n3.

The switching element 162 has a first end electrically connected to the common junction nd of the second transistor 157 and the third transistor 158, a second end, and a control for electrically connecting the output end of the anti-gate 161 end. The second end of each switching element 162 is electrically connected to the corresponding micro-electrode E1 E E900, and the switching element 162 is controlled according to the third intermediate signal n3 from the anti-gate 161. The switching element 162 is turned on or off to generate the microelectrode signal and the microelectrode signal is equal to the voltage level of the common junction nd. In this embodiment, the switching element 162 is an N-type metal oxide semiconductor (NMOS).

The second inverter gate 160 has an output terminal electrically connected to the first input end of the first multiplexer 151, and is electrically connected to the second transistor 157, the third transistor 158, and the switching element 162. The common junction nd input. The second inverter gate 160 reverses the logic value of the common contact nd to generate the measurement signal at the output.

Referring to FIG. 1, the wiring area 14 includes a data input pad (PAD) 141 electrically connected to the control unit CU1, a data output pad 142 electrically connected to the control unit CU900, and each control unit CU1~CU900 electrically connected. A clock pad 143, a first control pad 144, a second control pad 145 and a third control pad 146. The present invention utilizes a daisy chain (also referred to as a scan chain) to serially connect the output signals SO of the control units CU1 CU CU899 to the input signals SI of the adjacent control units CU2 CU 9000 , so that the biochip 1 The number of output pins can be greatly reduced. In addition, due to the reduction in the number of output pins, the wire bonding region 14 of the biochip 1 can be concentrated on one side of the biochip 1, and thus the second dielectric layer 122 of the cover 12, that is, glass, is on the biochip. In the process of 1, the complexity of positioning of the second dielectric layer 122 is effectively reduced to prevent the second dielectric layer 122 from crushing the bonding wires (not shown) on the bonding region 14 during the process.

The processing unit 2 is electrically connected to the data input of the wire bonding area 14 Pad 141, data output pad 142, clock pad 143, first control pad 144, second control pad 145, and third control pad 146, and the clock signal CLK, first control signal C1, second control signal C2 And the third control signal C3 is output to the control units CU1 CU CU 900 via the clock pad 143 , the first control pad 144 , the second control pad 145 , and the third control pad 146 , and the data input signal is The data input pad 141 is output to the control unit CU1, and receives a data output signal from the control unit CU900 via the data output pad 142.

It is particularly worth mentioning that in the embodiment, the processing unit 2 is disposed outside the bio-wafer 1, and in other embodiments, the processing unit 2 can also be integrated into the bio-wafer 1.

Referring to FIG. 4, the biochip 1 is based on the data input signal, the data output signal, the clock signal CLK, the first control signal C1, the second control signal C2, and the third control signal C3, in a driving mode and a sensing mode. operating. Hereinafter, for convenience of explanation, the driving mode will be described by taking a droplet 7 in the droplet space 128 and above the microelectrodes E50 to E51, E69 to 71, and E110 to E111 as an example.

Referring to FIG. 3 and FIG. 4, in the driving mode, the logic value of the first control signal C1 from the processing unit 2 is 0 by driving the droplet 7 to move in the direction of the microelectrodes E129 to E131. The D-type flip-flop 152 of the control unit CU1 sequentially stores the logical values of the data input signals in the D-type positive and negative of the control units CU900~CU1 according to the clock signal CLK and the data input signal from the processing unit 2. The logic value stored in the D-type flip-flop 152 of the control units CU129~CU131 is 1, The logic values stored in the D-type flip-flops 152 of the other control units CU1 CU CU 128 and CU 132 CU CU 900 are all zero.

The logic value of the second control signal C2 from the processing unit 2 is further changed to 1, so that the first transistor 156 and the second transistor 157 of each of the control units CU1 to CU900 are not turned on. Because the logic value of the first intermediate signal n1 of the control units CU129~CU131 is 1, the corresponding third transistor 158 and the switching element 162 are both turned on, resulting in the corresponding third transistor 158 respectively. The voltage level of E129~E131 is discharged to the second reference voltage V2, that is, 0 volt. The logic values of the first intermediate signal n1 of the other control units CU1~CU128, CU132~CU900 are all 0, so that the corresponding third transistor 158 and the switching element 162 are both non-conducting, resulting in the corresponding common contact nd. The logic value of the voltage level is kept at 1, and the corresponding microelectrodes E1~E128 and E132~E900 are kept in a floating state.

The third dielectric layer 123 receives a bias voltage, and the voltage level of the bias signal is between a predetermined voltage and the second reference voltage V2. In this embodiment, the preset voltage is 60 volts. Because the microelectrodes E1~E128 and E132~E900 are in a floating state, the voltage levels of the microelectrodes E1~E128 and E132~E900 are coupled by the bias signal, and are respectively related to the bias. The floating voltage of the voltage signal, however, the voltage levels of the microelectrodes E129~E131 can be maintained at the second reference voltage V2, that is, 0 volts, resulting in the first of the microelectrodes E1~E128, E132~E900. The electric field strength between the dielectric layer 121 and the second dielectric layer 122 and the first dielectric layer 121 and the second above the microelectrodes E129 to E131 The electric field strength in the middle of the dielectric layer 122 is different, and the droplets 7 located in the droplet space 128 are moved in the direction of the microelectrodes E129 to E131 under the influence of the electrowetting phenomenon to achieve the purpose of driving the sample.

Hereinafter, for convenience of explanation, the sensing mode will be described by taking N=3 and a droplet 7 is located in the droplet space 128 and above the microelectrode E2 as an example.

Referring to FIG. 3 and FIG. 5, FIG. 5 is a timing diagram of the first control signal C1, the second control signal C2, the third control signal C3, and the first intermediate signal n1 versus time in the sensing mode, and A timing diagram of the voltage level of the microelectrode versus time.

In the sensing mode, the voltage level of the bias signal is the second reference voltage V2, that is, 0 volts. Prior to time t1, the logic value stored by the D-type flip-flop 152 of each control unit CU1~CU3 has been reset to zero.

Between the times t1 and t2, the logic value of the first control signal C1 from the processing unit 2 is 1, so that the first multiplexer 151 of each control unit CU1~CU3 outputs the measurement signal received by the control unit 151 The output of the first multiplexer 151.

Between the times t2 and t3, the logic value of the second control signal C2 from the processing unit 2 is 1, so that the first intermediate signal n1, the second intermediate signal n2 and the third intermediate signal of each control unit CU1~CU3 The logic values of n3 are 0, 1, and 0, respectively, so that the first transistor 156, the second transistor 157, the third transistor 158, and the switching element 162 of each of the control units CU1 to CU3 are non-conducting. The voltage levels of each of the common contacts nd and the microelectrodes E1 to E3 are maintained at the first reference voltage V1.

The logic value of the third control signal C3 from the processing unit 2 is zero between times t3 and t4.

Between the times t4 and t5, the logic value of the second control signal C2 is 0, so that the logic values of the first intermediate signal n1, the second intermediate signal n2, and the third intermediate signal n3 of each control unit CU1~CU3 The first transistor 156, the second transistor 157, the third transistor 158, and the switching element 162 of each of the control units CU1 CU CU3 are respectively non-conducting, conducting, conducting, and conducting, and each The third transistor 158 of the control units CU1 CU CU3 discharges the corresponding microelectrodes E1 EE3 , which cause the voltage levels of the corresponding common contacts nd and the micro electrodes E1 EE3 to gradually decrease. At the same time, since the switching elements 162 of each of the control units CU1 to CU3 are turned on, the measurement signals thereof indicate the inverse of the logic values of the voltage levels of the corresponding microelectrodes E1 to E3.

Referring to FIG. 3, FIG. 5 and FIG. 6, FIG. 6 is an enlarged view of FIG. 5 between time t4 and time t6, and is a timing chart of the clock signal CLK, the first control signal C1, and the measurement signal versus time, and A timing diagram of the voltage level of the illustrated microelectrode versus time.

Between the times t4 and t41, when the logic value of the first control signal C1 is 1, the processing unit 2 outputs a clock pulse to the clock signal CLK, so that the measurement signals of each control unit CU1~CU3 are at t4. The logic value of the time is stored in the D-type flip-flop 152 of each of the control units CU1 to CU3.

Between the times t41 and t42, when the logic value of the first control signal C1 is 0, the processing unit 2 outputs two clock pulses to the clock signal CLK, so that the processing unit 2 receives the data output signal, and The logic values stored by the D-type flip-flops 152 of the control units CU3 CU1 are obtained.

The processing unit 2 repeatedly outputs the clock signal CLK and the first control signal C1 between t4 and t42, and sequentially stores the D-type flip-flops 152 of the control units CU3~CU1 at times t42, t44... Logic value, and until the logic value stored in each control unit CU1~CU3 is 1.

In the present embodiment, the time interval between t4 and t42, t42 and t44... is 1 nanosecond. The equivalent capacitance of the microelectrode E2 is about 21 femtofarads (fF), and the equivalent capacitance values of the microelectrodes E1 and E3 are about 13 fF. The processing unit 2 obtains that the logical values stored in each of the control units CU1 CU3 at times t4, t42, and t44 are (0, 0, 0), (1, 0, 1), and (1, 1, 1 respectively). After the calculation, it is found that the discharge times of the microelectrodes E1 to E3 are 1 nanosecond, 2 nanoseconds, and 1 nanosecond.

It is particularly worth mentioning that during the discharge process of each of the microelectrodes E1 to E3, that is, the first reference voltage V1 gradually falls between the second reference voltage V2, in general, the processing unit is The clock pulse generated by the clock signal CLK has a fixed pulse width, and the adjacent clock pulse also has a fixed time interval. Therefore, the processing unit can also calculate according to the time when the data output signal is sequentially read out. The discharge time of the microelectrodes E1 to E3 is as follows.

The processing unit 2 reads from the third control unit by using the clock signal CLK every time the level of the first control signal C1 is switched, to obtain a serial data having three output signals, and the first When the first control signal C1 is switched, the reading time points of each output signal are each taken as the initial discharge time of the corresponding microelectrodes E1 to E3. The processing unit 2 also changes the logical value of each output signal in the serial data as the end discharge time of the corresponding microelectrodes E1 to E3. The processing unit 2 obtains the discharge time corresponding to each of the microelectrodes E1 to E3 according to the initial discharge time and the end discharge time corresponding to each of the microelectrodes E1 to E3.

Between time t49 and time t5, the third transistor 158 of each control unit CU1~CU3 has discharged the corresponding microelectrode E1~E3 to the second reference voltage V2, that is, 0 volt.

Between the times t5 and t6, the logic values of the second control signal C2 and the third control signal C3 are 0 and 1, respectively, so that the first intermediate signal n1 and the second intermediate signal n2 of each control unit CU1 CU3 are And the logic values of the third intermediate signal n3 are 0, 0, and 1, respectively, so that the first transistor 156, the second transistor 157, the third transistor 158, and the switching element 162 of each of the control units CU1 CU3 respectively The first transistor 156 and the second transistor 157 of each of the control units CU1 CU CU charge the corresponding micro electrodes E1 EE3, resulting in corresponding common contacts nd and micro The voltage levels of the electrodes E1 to E3 gradually increase. At the same time, since the switching elements 162 of each of the control units CU1 to CU3 are turned on, the measurement signals thereof indicate the inverse of the logic values of the voltage levels of the corresponding microelectrodes E1 to E3.

Between the times t5 and t51, similar to the time between t4 and t41, when the logic value of the first control signal C1 is 1, the processing unit 2 outputs a clock pulse to the clock signal CLK, so that each control unit The logic value of the measurement signals of CU1~CU3 at time t5 is stored in each control list. The D-type flip-flop 152 of the CU1~CU3.

Between the times t51 and t52, similar to the time between t41 and t42, when the logic value of the first control signal C1 is 0, the processing unit 2 outputs two clock pulses to the clock signal CLK, so that the processing unit 2 receiving the data output signal, and sequentially obtaining the logic values stored by the D-type flip-flops 152 of the control units CU3 CU1.

The processing unit 2 repeatedly outputs the clock signal CLK and the first control signal C1 between t5 and t52, and sequentially stores the D-type flip-flops 152 of the control units CU3~CU1 at times t52, t54... Logic value, and until the logic value stored in each control unit CU1~CU3 is 0.

In the present embodiment, the time interval between t5 and t52, t52 and t54... is 1 nanosecond. The processing unit 2 obtains that the logical values stored in each of the control units CU1 CU3 at times t5, t52, and t54 are (1, 1, 1), (0, 1, 0), and (0, 0, 0, respectively). After calculation, it is known that the charging times of the microelectrodes E1 to E3 are 1 nanosecond, 2 nanoseconds, and 1 nanosecond.

It is particularly worth mentioning that during the charging process of each of the microelectrodes E1 to E3, that is, the second reference voltage V2 gradually rises to between the first reference voltage V1, in general, the processing unit is The clock pulse generated by the clock signal CLK has a fixed pulse width, and the adjacent clock pulse also has a fixed time interval. Therefore, the processing unit can also calculate according to the time when the data output signal is sequentially read out. The charging time of the microelectrodes E1 to E3 is as follows.

The processing unit 2 switches the first control signal C1 every time. During the calibration period, the clock signal CLK is used to read from the third control unit to obtain a serial data having three output signals, and each output signal is switched when the first control signal C1 is switched for the first time. The reading time points are each taken as the initial charging time of the corresponding microelectrodes E1 to E3. The processing unit 2 further changes the logic value of each output signal in the serial data as the end charging time of the corresponding microelectrodes E1 to E3. The processing unit 2 obtains the charging time corresponding to each of the microelectrodes E1 to E3 according to the initial charging time and the ending charging time corresponding to each of the microelectrodes E1 to E3.

The processing unit 2 obtains a voltage level change of each of the microelectrodes E1 to E3 according to the data output signal from the control unit CU3, and further calculates a charging time and a discharging time of each of the microelectrodes E1 to E3, and then according to the The difference between the discharge time, the charging time, and the discharge and charging time of the microelectrodes E1 to E3 is whether or not there is a droplet 7 above each of the microelectrodes E1 to E3 to achieve the purpose of sensing the position of the sample. Taking the droplet 7 of FIG. 4 as an example, the equivalent capacitance of the microelectrodes E50~E51, E69~E71, E110~E111 is about 21 flyFara, other microelectrodes E1~E49, E52~E68, E72~E109, The equivalent capacitance of E112~E900 is about 13fF. The charging time and discharge time of these microelectrodes E50~E51, E69~E71, E110~E111 will be greater than other microelectrodes E1~E49, E52~E68, E72~E109, E112. ~E900.

In addition, the processing unit 2 has a lookup table whose content is related to the relationship between the charging time and the discharging time of each of the plurality of types of samples corresponding to each of the microelectrodes E1 to E900. The processing unit 2 further outputs a discharge time, a charging time, or a discharge and a charging time of each of the microelectrodes E1 to E900 obtained according to the data output signal, and Comparing the contents of the lookup table, the type of the sample above each of the microelectrodes E1 to E900 can be known to achieve a mechanism for reading back the type of the sample.

It is known from the preferred embodiment that:

1. Since 900 control units CU1~CU900 are connected in series by means of daisy chain, only two input and output pins are provided to the control unit CU1 and the control unit CU900, and the remaining control units CU2~CU899 need not provide input and output. The bit can greatly reduce the number of input pins, so that the area of the biochip 1 is not limited by the number of input pins, and can be effectively utilized.

2. Using N control units to control the N microelectrodes, so that the droplets 7 located in the droplet space 128 can be accurately controlled in units of the area size of each microelectrode, not only effectively utilizing the sample but also providing analysis. Sensitivity, the driving path of the droplet 7 can be planned more according to the demand.

3. Using the processing unit 2, the position of the liquid droplet 7 can be judged simply and quickly, and the lookup table can be used again, that is, the type of the liquid droplet 7 can be judged, and the mechanism of readback can be realized.

4. The shielding layer 13 is used to effectively isolate the electromagnetic interference, so that the N control units can be respectively disposed under the N microelectrodes, and the bias signals of the cover 12 disposed above are prevented from interfering with the N control units.

In summary, the N control units are daisy-chained in series to greatly reduce the input and output signals, and the driving mode and the sensing mode are used to effectively drive and sense the sample, and the read-back sample is provided. The mechanism of the kind can indeed achieve the object of the present invention.

However, the above is only the preferred embodiment of the present invention, and the scope of the present invention cannot be limited thereto, that is, according to the present invention. The simple equivalent changes and modifications made by the scope of the patent application and the contents of the patent specification are still within the scope of the invention.

1‧‧‧Biochip

11‧‧‧Microelectrode dot array

12‧‧‧ Cover

14‧‧‧Line area

141‧‧‧data input pad

142‧‧‧ data output pad

143‧‧‧clock pad

144‧‧‧First control pad

145‧‧‧Second control pad

146‧‧‧ third control pad

2‧‧‧Processing unit

CLK‧‧‧ clock signal

C1‧‧‧ first control signal

C2‧‧‧second control signal

C3‧‧‧ third control signal

E1~E900‧‧‧Microelectrode

Claims (10)

A biochip comprising: an array of microelectrode dots, comprising N microelectrodes, N being an integer and N>1, the N microelectrodes being spaced apart from each other; a cover disposed above the array of microelectrode dots, Receiving a bias signal and including a droplet space for accommodating the droplet; a shielding layer disposed under the array of microelectrode dots for isolating electromagnetic interference from the cover to be transmitted thereto; and A control unit connected in series with N daisy chains is disposed under the shielding layer without electromagnetic interference from the cover body, and each control unit is located below the corresponding microelectrode, and each of the electrical connections corresponds to The microelectrode is configured to provide a microelectrode signal to the corresponding microelectrode, and each control unit receives a clock signal, a first to third control signal, and selects one according to the clock signal and the first control signal. An input signal or a measurement signal related to the microelectrode signal as an output signal, wherein an input signal received by a first one of the N control units is a data input for driving the droplet No. The input signals received by each of the remaining N-1 control units are each an output signal from a previous control unit, and each control unit also changes according to the second and third control signals and the output signal. The microelectrode signal is provided by using a differential pressure between the microelectrode signal and the bias signal between the different control units to drive droplets located in the droplet space of the cover. The biochip according to claim 1, according to the data input signal, the The clock signal, the first control signal, the second control signal, the third control signal, and the bias signal are operated in a driving mode, in the driving mode, if the droplet is above the k1 control unit When the droplet is driven to move over the adjacent k2 control unit, 1≦k1≦N,1≦k2≦N, so that the voltage level of the microelectrode of the k2 control unit is a second reference voltage. And the voltage level of the remaining microelectrodes is a floating voltage. The biochip of claim 1, wherein the cover further comprises: a first dielectric layer disposed above the array of microelectrode dots and having a first surface; and a second dielectric layer disposed at intervals Above the first dielectric layer, and having a second surface and a third surface on opposite sides, the first surface and the second surface being located between the first dielectric layer and the second dielectric layer; a second hydrophobic layer formed on the first surface of the first dielectric layer and the second surface of the second dielectric layer, wherein the two hydrophobic layers are between the droplet spaces; and a third dielectric layer is formed on the first surface a third surface of the dielectric layer and receiving the bias signal. The biochip of claim 1 further comprising: a hitting area comprising a data input pad electrically connected to the first one of the N control units, and an electrical connection of the N of the N control units a data output pad of the N control units, a clock pad electrically connected to the N control units, a first control pad, a second control pad, and A third control pad is disposed on one side of the array of microelectrode dots and is not located below the cover for use in the biochip wire package. A biodetection device comprising: a biochip comprising: a microelectrode dot array comprising N microelectrodes, N being an integer and N>1, the N microelectrodes being spaced apart from each other; a cover disposed at the a microelectrode dot array above and receiving a bias signal, and including a droplet space for accommodating the droplet; a shielding layer disposed under the microelectrode dot array for isolating the electromagnetic from the cover The interference is transmitted to the lower side; and the N daisy chain connection control unit is disposed under the shielding layer, each control unit is located below the corresponding microelectrode, and each of the corresponding microelectrodes is electrically connected Providing a microelectrode signal to the corresponding microelectrode, and each control unit receives a clock signal, a first to third control signal, and selects an input signal or a according to the clock signal and the first control signal a measurement signal related to the microelectrode signal as an output signal, wherein an input signal received by a first one of the N control units is a data input signal for driving the liquid droplet, Each of the input signals received by each of the N-1 control units is an output signal from its previous control unit, and each control unit also changes its provided according to the second and third control signals and the output signal. Microelectrode signal, use not a differential pressure between the microelectrode signal and the bias signal between the control unit to drive droplets located in the droplet space of the cover; and a processing unit electrically connected to the N control units and generating the data input signal a clock signal, a first control signal, a second control signal, and a third control signal, and receiving a data output signal, the data output signal being an output signal from an Nth control unit of the N control units, and The biochip is operated in a sensing mode to sense the position of the droplet based on the clock signal, the first control signal, the second control signal, the third control signal, and the data output signal. The biodetection device of claim 5, wherein, in the sensing mode, the processing unit sets the second and third control signals to control each microelectrode to be discharged from the first reference potential to the second reference a potential, the processing unit reads from the Nth control unit by using the clock signal during each switching of the level of the first control signal to obtain a serial data having N output signals, and The reading time points of each output signal when switching the first control signal are respectively used as the initial discharging time of the corresponding microelectrode, and the processing unit also changes the logical value of each output signal in the serial data as its The processing unit obtains a discharge time corresponding to each microelectrode according to an initial discharge time and an end discharge time corresponding to each microelectrode, and the processing unit sets the second and the second Three control signals to control each a microelectrode is charged to the first reference potential by the second reference potential, and the processing unit reads from the Nth control unit by using the clock signal during each switching of the level of the first control signal to Obtaining a serial data having N output signals, and each of the reading time points of each output signal is used as the initial charging time of the corresponding microelectrode when the first control signal is switched for the first time, and the processing unit further uses the string The logic value of each output signal in the column data changes, as the end charging time of the corresponding microelectrode, the processing unit obtains the corresponding microelectrode according to the initial charging time and the end charging time corresponding to each microelectrode. At a charging time, the processing unit determines whether there are droplets above the N microelectrodes based on the charging time, the discharging time, or the charging and discharging time of the N microelectrodes. The biometric detection device according to claim 6, wherein the processing unit has a lookup table, and the content of the lookup table is related to a relationship between charging time and discharge time of the plurality of different types of droplets corresponding to the N microelectrodes, the processing The unit also compares the discharge time, the charging time, or the discharge and charging time of the N microelectrodes with the contents of the lookup table to know the type of droplets above the N microelectrodes. The biodetection device of claim 5, wherein the biochip according to the data input signal, the clock signal, the first control signal, the second control signal, the third control signal, and the bias signal, Also operating in a drive mode, In the driving mode, if the droplet is above the k1 control unit, when the droplet is to be moved to move over the adjacent k2 control unit, 1≦k1≦N,1≦k2≦N, so that The voltage level of the microelectrode of the k2 control unit is a second reference voltage, and the voltage level of the remaining microelectrodes is a floating voltage. The biodetection device of claim 5, wherein the cover further comprises: a first dielectric layer disposed above the array of microelectrode dots and having a first surface; a second dielectric layer spaced apart The first dielectric layer and the second surface are disposed between the first dielectric layer and the second dielectric layer. And a second hydrophobic layer formed on the first surface of the first dielectric layer and the second surface of the second dielectric layer, the droplet space is between the two hydrophobic layers; and a third dielectric layer is formed on the second surface a third surface of the second dielectric layer and receiving the bias signal. The biometric device of claim 5, wherein the biochip further comprises a wire bonding zone, the wire bonding zone comprising a data input pad electrically connected to the processing unit and the first one of the N control units a data output pad electrically connected to the processing unit and the Nth control unit of the N control units, a clock pad electrically connected to the processing unit and the N control units, a first control pad, and a first control pad a second control pad, and a third control pad, the wire bonding area is disposed on one side of the micro electrode dot array And not located under the cover for use in the biochip wire package.